The present invention relates to novel polyoxypropylene-polyoxyethylene vitamin E and a method for preparing the same. More particularly, the present invention relates to amphipatic polyoxypropylenepolyoxyethylene vitamin E which is of high surface activity with excellent safety for the skin. Also, the present invention is concerned with the uses of such novel polyoxypropylenepolyoxyethylene vitamin E.
Generally, surfactants are adsorbed to the interfaces or surfaces of aqueous solutions to significantly reduce the interfacial tension or surface tension of the solutions. Depending on the concentration in a solution, surfactants form various types of micelles, which are an assembly of molecules or ions, of which advantage can be taken for various purposes.
The lipids which are of surface activity in vivo (bio-surfactants) play a role in regulating the physiological activities of organs and tissues. Bio-surfactants, which can be industrially manufactured, have useful purposes in a wide range of industries, including medicines, foods, cosmetics, etc., with classification into dispersants, emulsifiers, solubilizers, foaming agents, anti-foaming agents, polishing agents, slipping agents, surface-treating agents, wetting agents, etc. In addition to such function and purpose, ionic property is also a classification standard for surfactants, leading to ionic and non-ionic surfactants, and the latter may be further classified into hydrophilic and lipophilic surfactants. While the water solubility of ionic surfactants is attributed to the presence of ions in hydrophilic groups, non-ionic surfactants exhibit water solubility by virtue of their hydrogen bond with water.
It is known that the abundance of ionic materials in animal bodies forces non-ionic materials to be of higher bio-adaptability than ionic materials. In fact, non-ionic surfactants are generally used for the products which are applied to living bodies.
Hydrophilic non-ionic surfactants do not contain hydrophilic atomic groups which are ionized, and representative are those which have a hydroxy (xe2x80x94OH) group. Also, hydrophilic non-ionic surfactants may contain intramolecular ester bonds (xe2x80x94CO.Oxe2x80x94), acid amide bonds (xe2x80x94CO.NHxe2x80x94) and/or ether bonds (xe2x80x94Oxe2x80x94) although they all are weaker in hydrophilicity than a hydroxy group.
Of hydrophilic non-ionic surfactants, the most widely used and important are polyethylene glycol condensates which are exemplified by fatty acid polyethylene glycol condensates (Niosol, Myrj), fatty acid amide polyethylene glycol condensates, aliphatic alcohol polyethylene glycol condensates (Leonil, Peregal C), aliphatic amine polyethylene glycol condensates, aliphatic mercaptane polyethylene glycol condensates (Nyon 218), alkylphenyl polyethylene glycol condensates (Igepal), and polypropylene glycol polyethylene glycol condensates (Pluronics). Besides, various non-ionic surfactants which have complicated structures have recently been developed and utilized in various purposes, demonstrating their importance.
Generally, as aforementioned, ionic and non-ionic surfactants both are known to form micelles, which are an assembly of ions or molecules. As to why they form micelles, there are various differences between ionic surfactants and non-ionic surfactants. The formation of micelles is one of the most important properties which surfactants have, and is greatly affected by the structures of surfactants. Taking advantage of these properties, a great number of surfactants have been developed with their own purposes. The mechanism in which non-ionic surfactants form micelles in aqueous solutions can be revealed by the research on the surface tension, light diffusion and interaction with pigment of the micelles and other research. The cause of non-ionic surfactants forming micelles is the property in which the alkyl chains of the surfactant molecules are extricated from an aqueous phase by the adhesion force of water when they reach a critical concentration. In other words, the structure of a micelle is inherent in the structure of the non-ionic surfactant molecules, specifically in their amphipatic character. These properties and structural characteristics of non-ionic surfactants are primarily determined by the hydrophobic alkyl structure of the surfactant molecules. In fact, hydrophobic interactions are the major driving force for the formation of micelles or lipid bilayers.
The intensive and thorough research on new surfactants for skin care, repeated by the present inventors, led to the finding that, because vitamin E was well inserted into the ordered, dense lipid bilayers of cell membranes to protect the oxidation of the cell membranes, vitamin E played an efficient role as a hydrophobic group if it was applied to surfactants. As a result of the research, polyoxyethylene vitamin E was invented by subjecting vitamin E to addition reaction with ethylene oxide and patented with its high surface activity, skin soothing and moisturizing action, and cell protection from harmful active oxygen (Korean Pat. No. 083024, U.S. Pat. No. 5,235,073 and Japanese Pat. Appl""n No. Hei 4-10362). By virtue of its structural characteristics, the polyoxyethylene vitamin E is well absorbed into the interface, showing excellent surface activity. However, there is demanded an improvement in the safety for the skin. Because the hydrophobic, flat, hard chromane ring moiety piles up one by one neatly while the terminal phytyl group has a relatively small sectional area as well as fluidity, the polyoxyethylene vitamin E is too well inserted into the lipid bilayers of cell membranes, causing a problem in safety. This safety problem may be overcome by controlling the length of the ethylene oxide chain of the surfactant, that is, by extending the ethylene oxide chain. In this case, however, the polyoxyethylene vitamin E is too hydrophilic to exhibit a desirable surfactant function.
Typically, a surfactant consists of a hydrophobic atomic group and a hydrophilic atomic group with a balanced chemical linkage therebetween. Through intensive study, the present inventor recognized that most surfactants are structured to have hydrophobic atomic groups in one end and hydrophilic atomic groups in the other hand, but all are not. For instance, the non-ionic surfactant sold under the brand name xe2x80x9cPluronicsxe2x80x9d has polypropylene oxide as a hydrophobic atomic group, to both sides of which ethylene oxide is repetitively added (T. H. Vaughan, J. Am. Oil Chemists"" Soc. 2p, 240 (1950)), as represented by the following formula:
HO(C2H4O)a(C3H6O)b(C2H4O)cH
wherein a, b and c each is an integer of 20 to 80. Account is needed to be taken of special examples similar to this (Synthesis of Surfactants and Application thereof. P4.  (1956 Tokyo, Japan). Hydrophilicity prevails over hydrophobicity in ethylene oxide while propylene oxide is a little more hydrophobic than hydrophilic, so their polymers, polyethylene oxide and polypropylene oxide play a role as a hydrophilic atomic group and a hydrophilic atomic group, respectively, within a certain polymerization degree (Daves, J. T., Proc. 2nd Int. Congr. Surface Activity, London 1, 426 (1953)).
As a consequence of the active research which the present inventors have made on the constituents for cell membranes with the aim of developing surfactants which are greatly improved in the safety for the skin, it was perceived that phospholipids have diacyl as a hydrophobic group and exist at a significant quantity in all living microorganisms in addition to being important constituents for all cell membranes. Synthetic or natural phospholipids are commercially used to form liposomes or vesicles. Another important point which the inventors found out is that lysophospholipids, each of which contains an acyl group, are commercially used as emulsifiers by virtue of their superior surface activity to phospholipids themselves (J. L. Harwood and N. L. Russel, Lipids in Plants an Microbes, George Allen and Unwin, London, 1984). The formation of closed, bilayer liposomes or vesicles can be easily achieved by phospholipids, but difficultly by lysophospholipids.
Fatty acids, which are components of phospholipids, are safe materials and widely used in cosmetics, skin ointments, etc. However, fatty acid have strong toxic influence on cell membranes, so they are permitted to be used in a very low concentration range; elsewise, they may break cells occasionally. In phospholipids, fatty acids are linked via ester bonds whereas trace extracellular fatty acids are in a free state. Thus, fatty acids must be esterified at any rate if they exist in intracellular regions including the envelopes (Biosurfactants Surfactant Science Series p27, Vol. 48, 1993, New York, Marcel Dekker Inc.).
From the above fact, it is recognized that surfactants which are of diacyl phospholipid structure are inferior in general surface activity such as emulsification, but superior in the ability to form liposomes or cell membrane-like vesicles as well as especially in bio-safety to lysophospholipids which are of acyl type.
With the background of the invention in mind, the present inventors have conducted further research in improving the safety of the polyoxyethylene vitamin E while maintaining its high surface activity and finally found that, if a hydrophobic moiety is added to the end of the hydrophilic moiety of the polyoxyethylene vitamin E, the resulting compound has a controlled ratio of hydrophilic group to hydrophobic group and a different orientation characteristic. In this regard, the hydrophilic polyoxyethylene chain exists between two hydrophobic moieties, so the extended alkyl chain is converted from an almost linear state to a bent state, giving rise to an increase in the sectional area of the surfactant molecule. Consequently, the vitamin E prepared is a non-ionic amphipatic material which is of excellent surface activity with great improvement in safety for the skin. This material can be prepared by subjecting vitamin E to addition with a hydrophilic polyethylene oxide chain and a hydrophobic polypropylene oxide chain, in sequence, to such an extent that the ratio of the hydrophilic group to the hydrophobic group is suitable to form vesicles.
Therefore, it is an object of the present invention to provide a novel modified vitamin E which exhibits high surface activity with reliable safety for the skin.
It is another object of the present invention to provide a novel modified vitamin E which is useful in cosmetics, foods, medicines.
It is a further object of the present invention to provide a method for preparing such a novel modified vitamin E.
It is still a further object of the present invention to provide uses of such a novel modified vitamin E.
In accordance with an aspect of the present invention, there is provided novel polyoxypropylenepolyoxyethylene vitamin E, represented by the following general formula I: 
wherein,
R1 is xe2x80x94(OCH2CH2)mxe2x80x94 wherein m is an integer of 0 to 150;
R2 is 
xe2x80x83wherein n is an integer of 1 to 200;
A is 
xe2x80x83B is xe2x80x94CH3 at the 5-, 7- or 8-position of vitamin E; and
p is an integer of 1 or 3.
In accordance with another aspect of the present invention, there is provided a method for preparing the novel Polyoxypropylenepolyoxyethylene vitamin E, in which the vitamin E represented by the following general formula II, is subjected to addition reaction with ethylene oxide, represented by the following formula III, in the presence of a catalyst and then, with propylene oxide, represented by the following formula IV, in the presence of a catalyst: 
In accordance with a further aspect of the present invention, there is provided a skin care agent containing the novel polyoxypropylenepolyoxyethylene vitamin E.
In the present invention, the polyoxypropylenepolyoxyethylene vitamin E can be prepared from natural or synthetic vitamin E. In this regard, the vitamin E is subjected to polyethoxylation and then to polypropoxylation in the presence of a catalyst. It may be a Lewis acid catalyst or an alkaline catalyst. The polyoxypropylene polyoxyethylene vitamin E prepared is tested whether it functions well as a surfactant, an anti-oxidant and a skin care agent without harmful effects on the body. In this regard, it is evaluated for anti-oxidation activity by measuring its peroxide value, for foaming ability and foam stability by dynamic foam testing, for surface tension by the du Nuoy method, and for surface activity by the formation of vesicles. As for the safety in the human body, it is confirmed through eye irritation tests and patch tests.